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Epigenetic inactivation of PCDH10 in human prostate cancer cell lines.

机译:人前列腺癌细胞系中PCDH10的表观遗传失活。

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PCDH10 (protocadherin-10), a novel tumour suppressor gene, is down-regulated in several human cancers due to hypermethylation of promoter CGIs (CpG islands). Here, we investigated the expression of PCDH10 in different normal adult tissues and in a panel of prostate cancer cell lines. PCDH10 was widely expressed in normal tissues with higher levels in the prostate. The expression of PCDH10 was markedly reduced or silenced in prostate cancer cell lines compared with normal adult prostate tissue. Decreased PCDH10 expression was correlated with the methylation status of the PCDH10 promoter. Furthermore, the DNA demethylating agent 5'-azacytidin restored PCDH10 expression by suppressing PCDH10 promoter methylation in prostate cancer cell lines. Treatment with Trichostatin A alone had no significant effect on the expression of PCDH10 but enhanced the effect of 5'-azacytidin. In conclusion, we found that the decreased PCDH10 expression in prostate cancer cells was associated with the aberrant methylation of PCDH10 promoter CGI. Our results may contribute to the understanding of the role of PCDH10 inactivation in the progression of prostate cancers.
机译:PCDH10(protocadherin-10)是一种新型的肿瘤抑制基因,由于启动子CGI(CpG岛)的甲基化而在几种人类癌症中被下调。在这里,我们调查了PCDH10在不同的正常成人组织和一组前列腺癌细胞系中的表达。 PCDH10在前列腺中较高水平的正常组织中广泛表达。与正常成人前列腺组织相比,前列腺癌细胞系中PCDH10的表达明显降低或沉默。 PCDH10表达下降与PCDH10启动子的甲基化状态相关。此外,DNA去甲基化剂5'-氮杂胞苷通过抑制前列腺癌细胞系中的PCDH10启动子甲基化来恢复PCDH10的表达。单独用曲古他汀A处理对PCDH10的表达无明显影响,但增强了5'-氮杂胞苷的作用。总之,我们发现前列腺癌细胞中PCDH10表达的降低与PCDH10启动子CGI的异常甲基化有关。我们的结果可能有助于了解PCDH10失活在前列腺癌进展中的作用。

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